Study on the association of UGT1A9 gene c.98T>C polymorphism and mycophenolic acid plasma levels in renal transplant patients.

Mycophenolate mofetil (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms (SNPs) in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MMF. Expression levels and the activity of UGT1A9 may depend on the presence of some SNPs located in the gene promoter region (-2152C>T and -275T>A), as well as changes in the coding region (c.98T>C). The objective of this study was to evaluate the effect of allelic variants of the UGT1A9 c.98T>C polymorphism (rs72551330; g. 87289T>C) on MMF metabolism in renal transplant patients. MPA and MPA 7-O glucuronide (MPAG) levels were determined on plasma samples of kidney transplant patients (N = 39) by high-performance liquid chromatography using ultraviolet detection. DNA was isolated from leukocytes and stored at -20°C. The presence of SNPs was investigated using polymerase chain reaction, followed by amplicon sequencing. The analysis of the UGT1A9 c.98T>C polymorphism revealed that all study patients presented the TT genotype. Diverse MPA and MPAG plasma concentrations were detected, including therapeutic, subtherapeutic, and toxic levels. A standardized molecular method permitted identification of UGT1A9 c.98T>C polymorphism genotypes in the examined renal transplant patients. All individuals of the study group presented the same genotype (c.98TT) for that polymorphism. Thereby, no association between the c.98T>C polymorphism and MPA and MPAG plasma levels could be evaluated, despite different levels of these compounds being observed.

Procaína: Efeitos farmacológicos e toxicológicos / Procaine: Pharmacological and toxicological effects

Procaine is a local anesthetic used by dentists for decades. Nowadays it is being used to treat depression, increase the libido and act on inflammatory conditions and also to induce weight loss, among other uses. However, there has been criticism of such treatments with this substance, alone or in combination. The lack of a scientific basis makes its use subjective and unfounded and often potentially harmful to the individual. Therefore, the aim of this review is to find scientific evidence of systemic actions of procaine that demonstrate its efficacy for such purposes. From a review of the scientific literature, it was concluded that, except for a possible antidepressant effect, so far there are no data proving the alleged effects of procaine. In view of this, the current use of this substance in the treatment of chronic diseases or as an anti-aging drug would not be justified. Moreover, this review emphasizes the need for pharmacological and toxicological studies on procaine and the need to carry out in vivo and in vitro safety trials on pharmaceutical preparations containing this substance, in order to prove or disqualify the indications for its use.

A procaína é um anestésico local utilizado há décadas por dentistas. Atualmente, tem sido utilizada para tratar a depressão, aumentar a libido e agir em processos inflamatórios e no emagrecimento, entre outras utilidades. Porém, existem críticas acerca do tratamento com essa substância isolada ou associada. A falta de embasamento científico para sua utilização torna seu uso infundado e subjetivo, podendo ser muitas vezes nocivo ao indivíduo. Portanto, este artigo tem como objetivo buscar evidências científicas das ações sistêmicas da procaína que comprovem seus efeitos para tais finalidades. Foi realizado um levantamento na literatura científica e concluiu-se que, exceto por um possível efeito antidepressivo, até o momento não existem dados que comprovem os efeitos alegados para a procaína. Devido a isso, os usos atuais não se justificariam no tratamento de doenças crônicas ou no combate ao envelhecimento. Além disso, esta revisão enfatiza a necessidade da realização de estudos para avaliação farmacológica e toxicológica da procaína, bem como a necessidade de aplicar-se ensaios in vivo e in vitro na avaliação da segurança de preparações farmacêuticas que contenham essa substância, a fim de comprovar as inúmeras indicações de uso.

Sensitivity of young rats to nicotine exposure: Physiological and biochemical parameters.

This work has investigated the effects of prolonged exposure of young rats to nicotine on some physiological and biochemical parameters. Wistar male rats (30 days old) were treated (s.c.) with saline or nicotine 5mg/kg/day for 28 or 56 days. They received five injections (1mg/kg) per day (8, 10, 12:00 a.m., 2 and 4:00 p.m.) on the dark period of the cycle. Nicotine exposure for 56 days reduced body and liver weights. Moreover, nicotine exposure for 28 or 56 days decreased the hepatic glycogen but not blood glucose levels. The activities of blood and hepatic PBG-synthase, and blood and cerebral acetylcholinesterase were not affected by in vivo exposure. However, these activities were inhibited by nicotine in vitro. Results show that although high levels of plasma cotinine were found in both intervals of exposures, the parameters here analyzed were not affected by prolonged nicotine exposure except the storage of glucose, and body and liver weights.

Behavioral changes and cholinesterase activity of rats acutely treated with propoxur.

Early assessment of neurological and behavioral effects is extremely valuable for early identification of intoxications because preventive measures can be taken against more severe or chronic toxic consequences. The time course of the effects of an oral dose of the anticholinesterase agent propoxur (8.3 mg/kg) was determined on behaviors displayed in the open-field and during an active avoidance task by rats and on blood and brain cholinesterase activity. Maximum inhibition of blood cholinesterase was observed within 30 min after administration of propoxur. The half-life of enzyme-activity recovery was estimated to be 208.6 min. Peak brain cholinesterase inhibition was also detected between 5 and 30 min of the pesticide administration, but the half-life for enzyme activity recovery was much shorter, in the range of 85 min. Within this same time interval of the enzyme effects, diminished motor and exploratory activities and decreased performance of animals in the active avoidance task were observed. Likewise, behavioral normalization after propoxur followed a time frame similar to that of brain cholinesterase. These data indicate that behavioral changes that occur during intoxication with low oral doses of propoxur may be dissociated from signs characteristic of cholinergic over-stimulation but accompany brain cholinesterase activity inhibition.